Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: the effect of different substitution patterns.

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease.

Nutrigenomics: SNPs correlated to minerals' deficiencies.

Abstract: Nutrigenetics and nutrigenomics are two interrelated fields that explore the influence of genetic diversity on nutrient responses and function. While nutrigenetics investigates the effects of hereditary ge-netic variations on micronutrient metabolism, nutrigenomics examines the intricate relationship between diet and the genome, studying how genetic variants impact nutrient intake and gene expression. These disciplines offer valuable insights into predicting and managing chronic diseases through personalized nutritional approaches. Nutrigenomics employs cutting-edge genomics technologies to study nutrient-genome interactions. Key principles involve genetic variability among ethnic groups, affecting nutrient bioavailability and metabolism, and the influence of dietary choices based on cultural, geographic, and socioeconomic factors. Polymorphisms, particularly single-nucleotide polymorphisms (SNPs), significantly influence gene activity and are associated with specific phenotypes that are related to micronutrient deficiencies. Minerals are inorganic elements, vital for various physiological functions. Understanding the SNPs associated with mineral deficien-cies is crucial for assessing disease risk and developing personalized treatment plans. This knowledge can inform public health interventions, targeted screening programs, educational campaigns, and fortified food products to address deficiencies effectively. Nutrigenomics research has the potential to revolutionize clinical and nutritional practices, providing personalized recommendations, enhancing illness risk assessment, and advancing public health initiatives. Despite the need for further research, harnessing nutrigenomics' potential can lead to more focused and efficient methods for preventing and treating mineral deficiencies.

Nutrigenomics: SNPs Correlated to Lipid and Carbohydrate Metabolism.

Background: Nutrigenomics - the study of the interactions between genetics and nutrition - has emerged as a pivotal field in personalized nutrition. Among various genetic variations, single-nucleotide polymorphisms (SNPs) have been extensively studied for their probable relationship with metabolic traits. Methods: Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources. Results: SNPs have demonstrated a significant influence on lipid metabolism, by impacting genes that encode for enzymes involved in lipid synthesis, transport, and storage. Furthermore, they have the ability to affect enzymes in glycolysis and insulin signaling pathways: in a way, they can influence the risk of type 2 diabetes. Thanks to recent advances in genotyping technologies, we now know numerous SNPs linked to lipid and carbohydrate metabolism. The large-scale studies on this topic have unveiled the potential of personalized dietary recommendations based on an individual's genetic makeup. Personalized nutritional interventions hold promise to mitigate the risk of various chronic diseases; however, translating these scientific insights into actionable dietary guidelines is still challenging. Conclusions: As the field of nutrigenomics continues to evolve, collaborations between geneticists, nutritionists, and healthcare providers are essential to harness the power of genetic information for improving metabolic health. By unraveling the genetic basis of metabolic responses to diet, this field holds the potential to revolutionize how we approach dietary recommendations and preventive healthcare practices.

Nutrigenomics: SNPs correlated to detoxification, antioxidant capacity and longevity.

Abstract: Nutritional genomics, also known as nutrigenomics, is the study of how a person's diet and genes interact with each other. The field of nutrigenomics aims to explain how common nutrients, food additives and preservatives can change the body's genetic balance towards either health or sickness. This study reviews the effects of SNPs on detoxification, antioxidant capacity, and longevity. SNPs are mutations that only change one nucleotide at a specific site in the DNA. Specific SNPs have been associated to a variety of biological processes, including detoxification, antioxidant capacity, and longevity. This article mainly focuses on the following genes: SOD2, AS3MT, CYP1A2, and ADO-RA2A (detoxification); LEPR, TCF7L2, KCNJ11, AMY1, and UCP3 (antioxidant capacity); FOXO3 and BPIFB4 (longevity). This review underlines that many genes-among which FOXO3, TCF7L2, LEPR, CYP1A2, ADORA2A, and SOD2-have a unique effect on a person's health, susceptibility to disease, and general well-being. Due to their important roles in numerous biological processes and their implications for health, these genes have undergone intensive research. Examining the SNPs in these genes can provide insight into how genetic variants affect individuals' responses to their environment, their likelihood of developing certain diseases, and their general state of health.

Bioetics Issues of Artificial Placenta and Artificial Womb Technology.

Abstract: The worldwide infertility crisis and the increase in mortality and morbidity among infants, due to preterm births and associated complications, have stimulated research into artificial placenta (AP) and artificial womb (AW) technology as novel solutions. These technologies mimic the natural environment provided in the mother's womb, using chambers that ensure the supply of nutrients to the fetus and disposal of waste substances through an appropriate mechanism. This review aims to highlight the background of AP and AW technologies, revisit their historical development and proposed applications, and discuss challenges and bioethical and moral issues. Further research is required to investigate any negative effects of these new technologies, and ethical concerns pertaining to the structure and operation of this newly developed technology must be addressed and resolved prior to its introduction to the public sphere.

In Memory of Professor Derek Pheby.

Abstract: Professor Derek Pheby's passing in November 2022 marked a profound loss for the scientific community. Professor Derek Pheby, a stalwart figure in the fields of autoimmune diseases and bioethics, was known for his dedication to scientific research and patients' support, particularly for those affected by paraneoplastic autoimmune syndromes. Professor Pheby made significant contributions to research, especially about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). His leadership of the ME Biobank and scientific coordination of EUROMENE demonstrated his commitment to pushing boundaries and fostering international collaborations. Professor Pheby's scientific work addressed various aspects of ME/CFS, from physician education to patient needs, the development of a post-mortem tissue bank, and effective treatments. Beyond his medical career, Professor Pheby was a crucial member of the Independent Ethics Committee of MAGI, he was a poet, humanitarian, and advocate for child protection. His generosity and boundless spirit left an enduring legacy, fostering innovative research in the pursuit of combating autoimmune diseases.

Human Cloning: Biology, Ethics, and Social Implications.

Abstract: This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal implications. The exposition commences with a succinct historical and contextual overview of human cloning, segueing into an in-depth exploration of its biological intri-cacies. Central to this biological scrutiny is a comprehensive analysis of somatic cell nuclear transfer (SCNT) and its assorted iterations. The accomplishments and discoveries in cloning technology, such as successful animal cloning operations and advances in the efficiency and viability of cloned embryos, are reviewed. Future improvements, such as reprogramming procedures and gene editing technology, are also discussed. The discourse extends to ethical quandaries intrinsic to human cloning, entailing an extensive contemplation of values such as human dignity, autonomy, and safety. Furthermore, the ramifications of human cloning on a societal plane are subjected to scrutiny, with a dedicated emphasis on ramifications encompassing personal identity, kinship connections, and the fundamental notion of maternity. Culminating the analysis is a reiteration of the imperative to develop and govern human cloning technology judiciously and conscientiously. Finally, it discusses several ethical and practical issues, such as safety concerns, the possibility of exploitation, and the erosion of human dignity, and emphasizes the significance of carefully considering these issues.

Valorisation of softwood bark through extraction of utilizable chemicals. A review.

Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described. Finally, some challenges and perspectives on the production of chemicals from bark are discussed.

Immunoreactivity of chimeric proteins carrying the HIV-1 epitope IGPGRAF. Correlation between predicted conformation and antigenicity.

Sera from HIV-1 infected individuals were examined for their reactivity to the principal neutralizing domain, IGPGRAF sequence, of the V3-loop of HIV-1. Four hybrid proteins carrying this sequence inserted in four different outer loops of a protein that makes up the capsid of an insect virus were used as antigen in a Western blot assay for this survey. All the four antigens showed different activity: sera that recognise all antigens to sera that reacted with only one of them. Competition experiments indicated that the antibodies recognised these proteins with different affinity. Molecular modelling of the hybrid proteins predicted that the inserted sequence adopted different conformations in each position. Comparison of predicted most stable conformations for IGPGRAF indicated that there is a close relationship between conformational similarity to a V3-loop reference structure and the degree of reactivity with sera.

Design and synthesis of novel [60]fullerene derivatives as potential HIV aspartic protease inhibitors.

[structure] Two water-soluble fullerene derivatives have been computer-designed and synthesized. They may exhibit interesting anti-HIV activity owing to the presence of two ammonium groups strategically located on the spheroid surface.